Arur Swathi, Uche Uche E, Rezaul Karim, Fong Michael, Scranton Victoria, Cowan Ann E, Mohler William, Han David K
Center for Vascular Biology, Department of Physiology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, USA.
Dev Cell. 2003 Apr;4(4):587-98. doi: 10.1016/s1534-5807(03)00090-x.
Engulfment of apoptotic cells requires presentation of new cell surface ligands by the dying cells. Using a differential proteomics technology, we identify that annexin I is a caspase-dependent engulfment ligand; it is recruited from the cytosol and exported to the outer plasma membrane leaflet, colocalizes with phosphatidylserine, and is required for efficient clearance of apoptotic cells. Furthermore, phosphatidylserine receptor (PSR) clustering around apoptotic cells indicates a requirement for annexin I. In the nematode Caenorhabditis elegans, downregulation of the annexin homolog prevents efficient engulfment of pharyngeal cell corpses. These results provide novel mechanistic insights into how apoptotic cells are removed and may explain a pathogenic mechanism of chronic inflammatory diseases where annexin I autoantibodies have been described.
凋亡细胞的吞噬需要垂死细胞呈现新的细胞表面配体。利用差异蛋白质组学技术，我们确定膜联蛋白I是一种半胱天冬酶依赖性吞噬配体；它从细胞质中募集并输出到质膜外小叶，与磷脂酰丝氨酸共定位，是有效清除凋亡细胞所必需的。此外，凋亡细胞周围的磷脂酰丝氨酸受体（PSR）聚集表明对膜联蛋白I有需求。在线虫秀丽隐杆线虫中，膜联蛋白同源物的下调会阻止咽部细胞尸体的有效吞噬。这些结果为凋亡细胞如何被清除提供了新的机制见解，并可能解释了慢性炎症性疾病的一种致病机制，其中膜联蛋白I自身抗体已被描述。
